Development of a small animal model replicating core characteristics of takotsubo syndrome in humans.

Aims: Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models. Methods and results: We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning. Conclusion: This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.

Pheochromocytoma During Pregnancy: A Hidden Cause for Hypertension.

Pheochromocytoma, a rare but potentially serious condition, poses challenges in timely identification, especially during pregnancy due to misconceptions about pregnancy-related hypertension causes. However, paroxysmal symptoms heighten diagnostic suspicion. The diagnosis relies on biochemical confirmation of catecholamine hypersecretion followed by imaging for tumor localization. When diagnosed at or after 24 weeks, alpha-adrenoceptor blockers are recommended during pregnancy to manage catecholamine excess, delaying tumor removal until viability or post-delivery. The rarity of this condition during pregnancy, coupled with diagnostic and management challenges, underscores its importance for obstetric professionals in addressing hypertensive control, delivery timing, and surgical intervention.

The effect of the infusion connection point on intravenous multi-infusion drug delivery to premature neonates - Use of standard concentration infusions of critical medications.

BACKGROUND: Sick neonates with haemodynamic instability often require complex medication regimens, which may result in the connection of a catecholamine infusion distally. This increases the dead volume of the infusion system, extending the time to medication delivery. This study evaluated the effects of body weight, and infusion connection point on the delivery rate of two medications infused through a multi-infusion system at infusion rates suitable for extremely and very low birth weight (ELBW and VLBW) neonates. METHODS: An infusion system consisting of six infusions was used to investigate time to delivery, drug concentration at time to delivery and quantity of adrenaline and dopamine administered by intravenous infusions at infusion rates suitable for premature neonates. RESULTS: In an ELBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (66.7 (7.5)% (mean (SD)) and 68.0 (4.4)%, respectively, P < 0.001). At the calculated time to delivery, neither drug reached target concentration. In a VLBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (92.2 (7.1)% and 97.1 (3.1)%, respectively, P < 0.001). Adrenaline reached target concentration at 27 (11) min and dopamine at 56 (12) min, times significantly shorter than calculated. The measured quantity of adrenaline and dopamine delivered was lower (P < 0.001) than calculated in all tested combinations except adrenaline at proximal connection (97.2 (3.4)%, P = 0.097) in the VLBW neonate model CONCLUSIONS: Using the most proximal available infusion connection considerably improves drug delivery times and drug doses delivered, which is critical during the administration of short-acting cardiovascular medications.

Association between serum catecholamine levels and VNTR polymorphism in the promoter region of the monoamine oxidase A gene in forensic autopsy cases.

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.

Value of catecholamine levels in the differential diagnosis of vasovagal syncope and psychogenic pseudosyncope in children.

Background and purpose: Vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) can be difficult to distinguish, given their similar clinical presentations. This study was conducted to explore the clinical value of catecholamine levels in the differential diagnosis of VVS and PPS in children. Methods: This retrospective case-control study was conducted with data from children with VVS and PPS who underwent head-up tilt tests (HUTTs) at the Children's Hospital of Hebei Province between March 2021 and March 2023. The data collected were baseline clinical characteristics, HUTT results, serum catecholamine levels in the supine and upright positions, and 24 h urinary catecholamine concentrations. These variables were compared between the VVS and PPS groups. Results: From 328 potentially eligible cases, 54 (16.46%) cases of VVS and 24 (7.32%) cases of PPS were included in the analysis. No significant difference in age, sex, body mass index, or syncope frequency was observed between the VVS and PPS groups. The main predisposing factors for syncope were body position changes in the VSS group (83.33%) and emotional changes in the PPS group (41.67%). The episode duration was significantly shorter in the VSS group than in the PPS group (4.01 ± 1.20 vs. 24.06 ± 5.56 min, p < 0.05). The recovery time was also shorter in the VVS group than in the PPS group (1.91 ± 0.85 vs. 8.62 ± 2.55 min, p < 0.05). Relative to patients with PPS, those with VVS had significantly higher serum epinephrine (EP) levels in the upright position [199.35 (102.88, 575.00) vs. 147.40 (103.55, 227.25), p < 0.05] and lower serum epinephrine levels in the supine position [72.70 (42.92, 122.85) vs. 114.50 (66.57, 227.50), p < 0.05]. Conclusions: Serum EP levels have potential value in the differential diagnosis of VVS and PPS.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

A Case of Stress-Induced Cardiomyopathy After Ketamine Infusion.

We report the case of a 64-year-old female with a history of hypothyroidism and isolated parotid sarcoidosis who presented with acute-onset chest pain and dyspnea. Echocardiogram demonstrated transiently reduced ejection fraction with apical hypokinesis, without evidence of obstructive coronary lesions on angiography, compatible with stress-induced cardiomyopathy. She received a ketamine infusion as a mental health treatment shortly before the development of symptoms, suggesting that this medication may have precipitated her cardiomyopathy. In recent years, ketamine has become a popular option for treating mental health disorders, including major depressive disorder and substance use disorders. It should be used with caution in patients with known cardiovascular disease, and its cardiac effects warrant further study.

Optical Control of Cell-Surface and Endomembrane-Exclusive ß-Adrenergic Receptor Signaling.

Beta-adrenergic receptors (ßARs) are G protein-coupled receptors (GPCRs) that mediate catecholamine hormone-induced stress responses, such as elevation of heart rate. Besides those that are plasma membrane-bound, endomembrane ßARs are also signaling competent. Dysregulation of ßAR pathways underlies severe pathological conditions. Emerging evidence indicates pathological molecular signatures in deeper endomembrane ßARs signaling, likely contributing to conditions such as cardiomyocyte hypertrophy and apoptosis. However, the lack of approaches to control endomembrane ß1ARs has impeded linking signaling with pathology. Informed by the ß1AR-catecholamine interactions, we engineered an efficient photo-labile pro-ligand (OptoIso) to trigger ßAR signaling exclusively in endomembrane regions using blue light stimulation. Not only does OptoIso undergo blue light deprotection in seconds, but also efficiently enters cells and allows examination of G protein heterotrimer activation exclusively at endomembranes. OptoIso also allows optical activation of plasma membrane ßAR signaling in selected single cells with native fidelity, which can be reversed by terminating blue light. Thus, OptoIso will be a valuable experimental tool to elicit spatial and temporal control of ßAR signaling in user-defined endomembrane or plasma membrane regions in unmodified cells with native fidelity.

Automated online solid-phase extraction-tandem mass spectrometry detection for simultaneous analysis of acidic and alkaline catecholamines and their metabolites in human urine.

Metabolic dysregulation of catecholamines (CAs) is implicated in various human diseases. Simultaneously analyzing these acidic and alkaline CAs and their metabolites poses a significant challenge for clinical detection. This study introduces an efficient method employing automated online solid-phase extraction coupled with tandem mass spectrometry (aoSPE-MS/MS). The method employs weak cation exchange (WCX) and mixed-mode anion exchange (MAX) adsorbents to fabricate an on-line solid-phase extraction (SPE) column, along with an automated injection and multi-valve switching capabilities. The setup allows for automated extraction and analysis of urine samples in 15 minutes while retaining a wide range of acidic and basic CAs and their metabolites. The applicability of this method was demonstrated by optimising the adsorbent dosage volume, extraction solvent, and extraction rate. The limits of detection (LODs) and limits of quantitation (LOQs) for the 8 CAs and their metabolites were determined using the aoSPE-MS/MS approach, with ranges of 0.0625 ∼ 62.5 ng/mL and 0.125 ∼ 125 ng/mL, respectively. Additionally, assessments were made on the linearity, accuracy, and precision within and between batches, as well as matrix and ionic effects, and spiked recoveries. The study discovered that the aoSPE-MS/MS technique simplifies operation, increases efficiency, saves time, and has low detection and quantification limits when detecting a wide range of acid and alkaline CAs and their metabolites in urine. The study successfully demonstrated the high-throughput and automated detection of the 8 CAs and their metabolites with varying acidity and alkalinity in human urine samples. This method is expected to be a potential powerful tool for clinical detection.

Polydopamine Adhesion: Catechol, Amine, Dihydroxyindole, and Aggregation Dynamics.

While polydopamine (PDA) possesses the surface-independent adhesion property of mussel-binding proteins, significant differences exist between them. Particularly, PDA's short and rigid backbone differs from the long and flexible protein sequence of mussel-binding proteins. Given that adhesion relies on achieving a conformal contact with large surface coverage, PDA has drawbacks as an adhesive. In our study, we investigated the roles of each building block of PDA to build a better understanding of their binding mechanisms. Initially, we anticipated that catecholamine oligomers form specific binding with substrates. However, our study showed that the universal adhesion of PDA is initiated by the solubility limit of growing oligomers by forming agglomerates, complemented by multiple binding modes of catechol. Notably, in the absence of amines, poly(catechol) either remained in solution or formed minor suspensions without any surface coating, underscoring the essential role of amines in the adhesion process by facilitating insoluble aggregate formation. To substantiate our findings, we induced poly(catechol) aggregation using quaternized poly(4-vinylpyridine) (qPVP), leading to subsequent surface adhesion upon agglomerate formation.

Diabetic Ketoacidosis: A Rare Complication of Type 3c Diabetes.

Recently termed pancreoprivic diabetes, type 3c diabetes refers to high blood sugar values secondary to disease of the exocrine pancreas. The disease is most commonly misdiagnosed as type 2 diabetes mellitus (DM) and is overlooked by physicians and the general public. Chronic pancreatitis (CP) accounts for most cases of type 3c diabetes. Diabetic ketoacidosis (DKA) is a rare occurrence in type 3c diabetes as both alpha and beta cell dysfunction occur concurrently. In this case, the major hormones involved in lipolysis and ketone body production would be catecholamines, cortisol, and growth hormone. We report a case of a 37-year-old female with a history of endocrine pancreatic insufficiency secondary to CP who presented with DKA, one of the life-threatening but preventable complications of diabetes. Noncompliance with insulin and concurrent urinary tract infection were the inciting factors. Her condition improved with DKA management according to standard protocol, intravenous antibiotics, and other supportive care. She got discharged after optimization of insulin therapy, with proper advice for home blood sugar monitoring and regular follow-up. A patient with pancreatic pathology may present to the emergency with DKA as the first manifestation, and if not properly evaluated, the diagnosis of type 3c diabetes can be missed.

Differential Modulation of Catecholamine and Adipokine Secretion by the Short Chain Fatty Acid Receptor FFAR3 and α2-Adrenergic Receptors in PC12 Cells.

Sympathetic nervous system (SNS) hyperactivity is mediated by elevated catecholamine (CA) secretion from the adrenal medulla, as well as enhanced norepinephrine (NE) release from peripheral sympathetic nerve terminals. Adrenal CA production from chromaffin cells is tightly regulated by sympatho-inhibitory α2-adrenergic (auto)receptors (ARs), which inhibit both epinephrine (Epi) and NE secretion via coupling to Gi/o proteins. α2-AR function is, in turn, regulated by G protein-coupled receptor (GPCR)-kinases (GRKs), especially GRK2, which phosphorylate and desensitize them, i.e., uncouple them from G proteins. On the other hand, the short-chain free fatty acid (SCFA) receptor (FFAR)-3, also known as GPR41, promotes NE release from sympathetic neurons via the Gi/o-derived free Gßγ-activated phospholipase C (PLC)-ß/Ca2+ signaling pathway. However, whether it exerts a similar effect in adrenal chromaffin cells is not known at present. In the present study, we examined the interplay of the sympatho-inhibitory α2A-AR and the sympatho-stimulatory FFAR3 in the regulation of CA secretion from rat adrenal chromaffin (pheochromocytoma) PC12 cells. We show that FFAR3 promotes CA secretion, similarly to what GRK2-dependent α2A-AR desensitization does. In addition, FFAR3 activation enhances the effect of the physiologic stimulus (acetylcholine) on CA secretion. Importantly, GRK2 blockade to restore α2A-AR function or the ketone body beta-hydroxybutyrate (BHB or 3-hydroxybutyrate), via FFAR3 antagonism, partially suppress CA production, when applied individually. When combined, however, CA secretion from PC12 cells is profoundly suppressed. Finally, propionate-activated FFAR3 induces leptin and adiponectin secretion from PC12 cells, two important adipokines known to be involved in tissue inflammation, and this effect of FFAR3 is fully blocked by the ketone BHB. In conclusion, SCFAs can promote CA and adipokine secretion from adrenal chromaffin cells via FFAR3 activation, but the metabolite/ketone body BHB can effectively inhibit this action.

Cardiogenic pulmonary edema - is it lone cardiogenic? "Missing link" between hemodynamic and other existing mechanisms.

The current traditional pathophysiologic concept of pulmonary edema of cardiogenic origin explains its development by a hydrostatic effect due to increased pulmonary capillary pressure resulting in fluid flux to alveolar and interstitial areas from capillaries. However, several experimental studies and clinical data of poor response to hemodynamic and diuretic treatment in many scenarios provide further evidence of the involvement of several other contributing factors to the development of cardiogenic pulmonary edema. Several experimental and clinical studies have found that sympathetic overactivity with elevated plasma catecholamine concentrations may play an important role in the development of cardiovascular-associated pulmonary edema. Catecholamine-induced pulmonary injury may be one of the key mechanisms in acute cardiogenic pulmonary edema triggering proinflammatory cytokine overactivation, oxidative stress and myocardial injury. In the everyday treatment of acute heart failure, physicians should consider the possibility of other noncardiogenic mechanisms involved in the progression of acute pulmonary edema, particularly catecholamine overactivity, lymphatic drainage, inflammatory and oxidative stress, high surfactant protein. The classic, hemodynamic treatment approach in pulmonary edema with the coexistence of other contributing factors may not provide adequate clinical benefit during treatment.

Cushing Syndrome Due to a Corticotropin-Releasing Hormone- and Adrenocorticotropic Hormone-Secreting Silent Pheochromocytoma.

Background/Objective: Ectopic cosecretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in silent (ie, non-catecholamine-secreting) pheochromocytoma is a rare cause of Cushing syndrome. Case Report: A 57-year-old woman rapidly developed hypercortisolism, clinically manifesting as fatigue, muscle weakness, weight gain, and worsening hypertension and biochemically characterized by hypokalemia and marked increases in the serum cortisol and plasma ACTH levels. This acute presentation suggested a diagnosis of ectopic ACTH syndrome (EAS). Imaging studies revealed a right adrenal mass that enhanced after administration of the radioisotope gallium-68-DOTATATE. Plasma metanephrines were normal in 2 separate measurements. The possibility of a silent pheochromocytoma was considered. After controlling her hypercortisolism with metyrapone and surgical preparation with alpha blockade, the patient underwent elective right adrenalectomy. Pathology revealed a pheochromocytoma that stained focally for ACTH and CRH. Postoperatively, the cortisol levels normalized, the hypothalamic-pituitary-adrenal axis was not suppressed, and clinical symptoms from hypercortisolism abated. Discussion: Patients who exhibit a rapid progression of ACTH-dependent hypercortisolism should be screened for EAS. The use of functional imaging radioisotopes (eg, gallium DOTA-peptides) improves the detection of ACTH-secreting tumors. Preoperative treatment with steroidogenesis inhibitors helps control clinical and metabolic derangements associated with severe hypercortisolemia, whereas alpha blockade prevents the onset of an adrenergic crisis. Conclusion: We present a rare case of EAS due to a silent pheochromocytoma that cosecreted ACTH and CRH. Pheochromocytoma should be considered in patients with EAS who have an adrenal mass even in the absence of excessive catecholamine secretion.

Molecular characterization and distribution of motilin and motilin receptor in the Japanese medaka Oryzias latipes.

Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes). Quantitative PCR revealed that mln mRNA was limitedly expressed in the gut, whereas mlnr mRNA was not detected in the gut but was expressed in the brain and kidney. By in situ hybridization and immunohistochemistry, mlnr mRNA was detected in the dopaminergic neurons of the area postrema in the brain and the noradrenaline-producing cells in the interrenal gland of the kidney. Furthermore, we observed efferent projections of mlnr-expressing dopaminergic neurons in the lobus vagi (XL) and nucleus motorius nervi vagi (NXm) of the medulla oblongata by establishing a transgenic medaka expressing the enhanced green fluorescence protein driven by the mlnr promoter. The expression of dopamine receptor mRNAs in the XL and cholinergic neurons in NXm was confirmed by in situ hybridization. These results indicate novel sites of MLN activity other than the gastrointestinal tract. MLN may exert central and peripheral actions through the regulation of catecholamine release in medaka.

Obesity-induced tissue alterations resist weight loss: A mechanistic review.

Interventions aimed at weight control often have limited effectiveness in combating obesity. This review explores how obesity-induced dysfunction in white (WAT) and brown adipose tissue (BAT), skeletal muscle, and the brain blunt weight loss, leading to retention of stored fat. In obesity, increased adrenergic stimulation and inflammation downregulate ß-adrenoreceptors and impair catecholaminergic signalling in adipocytes. This disrupts adrenergic-mediated lipolysis, diminishing lipid oxidation in both white and brown adipocytes, lowering thermogenesis and blunting fat loss. Emerging evidence suggests that WAT fibrosis is associated with worse weight loss outcomes; indeed, limiting collagen and laminin-α4 deposition mitigates WAT accumulation, enhances browning, and protects against high-fat-diet-induced obesity. Obesity compromises mitochondrial oxidative capacity and lipid oxidation in skeletal muscle, impairing its ability to switch between glucose and lipid metabolism in response to varying nutrient levels and exercise. This dysfunctional phenotype in muscle is exacerbated in the presence of obesity-associated sarcopenia. Additionally, obesity suppresses sarcolipin-induced sarcoplasmic reticulum calcium ATPase (SERCA) activation, resulting in reduced oxidative capacity, diminished energy expenditure, and increased adiposity. In the hypothalamus, obesity and overnutrition impair insulin and leptin signalling. This blunts central satiety signals, favouring a shift in energy balance toward energy conservation and body fat retention. Moreover, both obese animals and humans demonstrate impaired dopaminergic signalling and diminished responses to nutrient intake in the striatum, which tend to persist after weight loss. This may result in enduring inclinations toward overeating and a sedentary lifestyle. Collectively, the tissue adaptations described pose significant challenges to effectively achieving and sustaining weight loss in obesity.

Gastric paraganglioma: a case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

A case report on pheochromocytoma mimicking as fulminant myocarditis-a diagnostic challenge.

We present an exceptional case of a 53-year-old female, initially misdiagnosed with fulminant myocarditis, but later correctly diagnosed with pheochromocytoma. The presentation of the patient included a spectrum of symptoms such as headache, chest discomfort, palpitations, and dyspnea, following the intake of Domperidone. Two weeks prior to admission, the patient had experienced episodes of diarrhea and a low-grade fever. Unresolved symptoms and an unmanageable surge in blood pressure despite comprehensive fulminant myocarditis treatment prompted further investigation. The discovery of an adrenal mass via a CT scan and subsequent biochemical tests led to the confirmation of pheochromocytoma. Implementation of alpha-blockade therapy and a successful laparoscopic adrenalectomy resulted in significant clinical improvement. This case underscores the diagnostic intricacies of pheochromocytoma and highlights the need for vigilance when faced with severe, unresponsive cardiovascular symptoms.

Managing Catecholamine Release Syndrome During and Following Lu-177-DOTATATE in High-Risk Pheochromocytoma Patients.

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing tumors that express somatostatin receptors (SSTR) that can be treated with lutetium-177 DOTATATE (Lu-177-TRT); however, treatment can be associated with life-threatening cardiovascular events. A patient case with management strategies for high-risk PPGL patients receiving Lu-177-TRT is described. The 78-year-old patient with metastatic paraganglioma was enrolled and treated under NCT03206060. Deemed to be at high risk, the patient was preemptively admitted to the intensive care unit (ICU) with central line access placed. Due to comorbidities, a reduced dose of 100 mCi x 4 cycles was used for this patient. Vital signs, blood work, and serum catecholamine levels were obtained at various time points. Despite reduced dosing, the patient still developed a severe hypertensive reaction with systolic blood pressure of 240 mmHg within minutes of Lu-177-TRT infusion, which was controlled with an intravenous nicardipine drip. The patient remained in the ICU for 24 hours post Lu-177-TRT before moving to an inpatient ward for an additional 24 hours. All subsequent infusions were performed using reduced doses with elective ICU admissions and were well-tolerated. Despite the increased risk, metastatic PPGL patients can be safely treated with proper staff training, monitoring, and preparation for intravenous medications, especially nicardipine.

Recurrent angina and cardiac ischaemia as a presentation of pheochromocytoma: a case report.

Background: We present a case of a pregnant patient with recurrent angina, in which her symptoms were initially attributed to coronary artery spasm. However, during follow-up, she was diagnosed as having pheochromocytoma, a rare neuroendocrine tumour. Case summary: The 35-year-old patient was admitted to the hospital because of chest pain and elevated cardiac troponins after the use of MDMA. Physical examination, electrocardiogram, echocardiography, coronary angiogram, and cardiac MRI were normal. Symptoms were attributed to coronary spasm, and a calcium antagonist was started. Ten months later, when 36 weeks pregnant, her symptoms returned. One week later, the patient was readmitted to the hospital with signs of acute left ventricular (LV) failure, highly elevated troponins, and severe global LV dysfunction. Urgent section caesarean was performed due to maternal morbidity and foetal tachycardia. During section, flushes and marked variability in blood pressure were noted. Laboratory metanephrines testing was performed. LV function recovered within 3 days without any therapeutic intervention. However, chest pain reoccurred, now accompanied with headaches, malignant hypertension, and accelerated idiopathic ventricular rhythms. (Nor)metanephrines tests were positive. A solid lesion in the right adrenal on CT scan confirmed the diagnosis of pheochromocytoma. Fluid repletion and alpha-blocker therapy were started. Due to persistent symptoms, urgent laparoscopic adrenalectomy was performed. Hereafter, the patient remained without symptoms. Discussion: A pheochromocytoma may present with recurrent angina and can result in a catecholamine-induced cardiomyopathy. It is important to timely recognize this diagnosis in order to minimize morbidity and mortality.